Our goal is to characterize and localize the hormones and mechanisms active in rat and mouse brain in neuroendocrine and behavioral sexual differentiation during the perinatal period, and in sexual and fighting behavior during adulthood. Radioimmunoassay and systemic and intracerebral implantation will be used to measure, administer and localize the effects of possible sexual differentiating agents. Anti-hormones and other drugs will be used to extend these findings. Tests of effectiveness will include vaginal cyclicity, ovarian luteinization, phallic sensitization to androgens, saccharine preference, muricide and emergence, open-field, sexual and fighting behaviors. Our previous work suggested that testosterone (T) and androstenedione (A) were equally effective in neuroendocrine, but ineffective in sexual behavioral, sexual differentiation. Dihydrotestosterone (DHT) was ineffective in both systems, while T, A and DHT all produced clitoral sensitization to androgens. The proposed research tests the hypothesis that different hormones act in different sexually differentiated systems. Systemic and intracerebral administration of estradiol (E2), estrone (E1), anti-estrogens and protein synthesis inhibitors will be used to characterize and localize the estrogenic control of sexual receptivity. Our previous work indicated that H3-E2 and H3-E1 were both accumulated by the brain, but their distribution patterns were different. In pilot work we found that E2 and E1 both induced sexual receptivity, suggesting that E2 and E1 may normally work in concert possibly through actions in different regions of the brain. Our H3-progesterone work has suggested a mesencephallic site of action and future systemic and intracerebral implantation work will explore this possibility in sexual and fighting behaviors. In similar studies we will characterize and localize the sites of androgen action in these behaviors. In earlier work we found that T and A were equally effective in male rat sexual behavior, while DHT was ineffective. Back-up studies will explore H3-hormone localization, retention, saturation, reversibility, subcellular distribution and metabolism in the brain. Hormone effects on rates of intracerebral protein synthesis will also be explored.